title: Leflunomide suppresses growth in human medullary thyroid cancer cells.
abstract: BACKGROUND
  Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Leflunomide (LFN) is a disease-modifying antirheumatic drug approved for the treatment of rheumatoid arthritis, and its active metabolite teriflunomide has been identified as a potential anticancer drug. In this study we investigated the ability of LFN to similarly act as an anticancer drug by examining the effects of LFN treatment on MTC cells.
  
  
  METHODS
  Human MTC-TT cells were treated with LFN (25-150 μmol/L) and Western blotting was performed to measure levels of neuroendocrine markers. MTT assays were used to assess the effect of LFN treatment on cellular proliferation.
  
  
  RESULTS
  LFN treatment downregulated neuroendocrine markers ASCL1 and chromogranin A. Importantly, LFN significantly inhibited the growth of MTC cells in a dose-dependent manner.
  
  
  CONCLUSIONS
  Treatment with LFN decreased neuroendocrine tumor marker expression and reduced the cell proliferation in MTC cells. As the safety of LFN in human beings is well established, a clinical trial using this drug to treat patients with advanced MTC may be warranted.
authors.affiliation: Endocrine Surgery Research, Department of Surgery, University of Wisconsin, and Carbon Cancer Center, Madison, Wisconsin.
authors.forename: Amal
authors.initials: A
authors.lastname: Alhefdhi
authors.forename: Jocelyn F
authors.initials: JF
authors.lastname: Burke
authors.forename: Aaron
authors.initials: A
authors.lastname: Redlich
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Kunnimalaiyaan
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053379:Chromogranin A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D018501:Antirheumatic Agents; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D053379:Chromogranin A; D007555:Isoxazoles; D000077339:Leflunomide; C065500:ASCL1 protein, human
keywords: Leflunomide (LFN); Medullary thyroid cancer (MTC); Neuroendocrine tumors